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Nevin Manimala Statistics

Anticoagulant drugs with or without proton pump inhibitor and colorectal cancer risk: a population-based, case-control study

BMC Gastroenterol. 2022 May 9;22(1):225. doi: 10.1186/s12876-022-02314-w.

ABSTRACT

BACKGROUND: Low-dose aspirin and clopidogrel have demonstrated potential chemoprevention for colorectal cancer (CRC). Proton-pump inhibitors (PPI) are commonly prescribed with anticoagulation drugs, but the relationship between PPI and CRC is unclear. Moreover, evidence of CRC risk under direct oral anticoagulant (DOAC) is limited. This study aimed to investigate the effects of anticoagulation drugs combined with or without PPI on the risks of CRC in Taiwan.

METHODS: A retrospective case-control study of 1,024,227 cases based on the Chang Gung Research Database from 2010 to 2017 was performed. Clinical characteristics, indications, duration of anticoagulation and PPI use, and CRC occurrence data were collected. Logistic regression was employed to adjust for known confounders of CRC risk.

RESULTS: Monotherapy of clopidogrel decreased the risk of CRC (AOR 0.70; 95% CI 0.60-0.83), while no protective effect was observed in aspirin alone or aspirin plus clopidogrel. DOAC did not affect CRC significantly. The risk of CRC increased in patients with PPI (AOR 1.38; 95% CI 1.28-1.49) and PPI plus DOAC (OR 3.91; 95% CI 1.49-10.27), while PPI plus aspirin decreased the risk of CRC (OR 0.48; 95% CI 0.32-0.73). PPI plus clopidogrel showed no significant effect on the CRC.

CONCLUSION: This study suggests clopidogrel alone and PPI plus aspirin offer a preventative benefit against CRC in the Taiwanese population studied. The same effect was not observed in DOAC. Moreover, a significant increase in CRC was observed in patients on PPI monotherapy and PPI plus DOAC, suggesting a possible risk.

PMID:35534834 | DOI:10.1186/s12876-022-02314-w

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Nevin Manimala Statistics

Blood pressure control status of patients with hypertension on treatment in Dessie City Northeast Ethiopia

BMC Public Health. 2022 May 9;22(1):917. doi: 10.1186/s12889-022-13368-6.

ABSTRACT

INTRODUCTION: Uncontrolled blood pressure contributes a huge contribution to many hypertension-related complications and it is one of the unbeaten problems for patients taking antihypertensive drugs. The association of social support and other factors with uncontrolled blood pressure during the covid-19 pandemic is not well investigated. Therefore, this study explored the determinants of blood pressure control status during the COVID-19 pandemic among patients with hypertension who were on an antihypertensive treatment.

METHOD: A cross-sectional study was done from March to May 2021 among adults aged 18 or more patients with hypertension for three months or more on treatment in Dessie City. An interview-administered questionnaire was done using simple random sampling from hypertension follow-up register for 380 patients with hypertension. Blood pressure measurement was taken from their arm using a stethoscope and mercury sphygmomanometer at a sitting position with 90-degree back support. Uncontrolled blood pressure was also computed either the systolic or diastolic blood pressure greater than or less than the limit of uncontrolled blood pressure with regarding the age and diabetic status of patients. The perceived social support-related questionnaire was adopted from the Multidimensional Scale of Perceived Social Support (MSPSS) -12 item checklist. It was sum-up and transformed into three categories using tertile of their computed raw scores. The adjusted prevalence ratio with a 95 percent confidence interval (CI) was used to calculate the strength of the association between uncontrolled blood pressure and independent predictors using log-binomial regression analysis. A P-value less than 0.05 was declared as statistically significant in multivariable log-binomial regression analysis.

RESULT: A total of 360 study participants were included in this study. The prevalence of uncontrolled blood measures in patients with hypertension with a 95% CI was 55.8(50.7, 61.0). In a multivariable analysis adjusted prevalence ratio with 95% CI for poor medication adherence 1.86(1.59,2.19), being male 1.35(1.11,1.64), secondary education 0.52(0.35,0.77), and low social support 1.24(1.01, 1.54) were the predictors of uncontrolled blood pressure.

CONCLUSION: Uncontrolled blood pressure for patients with hypertension on treatment is higher during the COVID-19 pandemic. Being male, poor medication adherence, educational status and low social support are factors that contribute to uncontrolled blood pressure.

PMID:35534831 | DOI:10.1186/s12889-022-13368-6

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Nevin Manimala Statistics

Sick leave and disability pension in a cohort of TMD-patients – The Swedish National Registry Studies for Surgically Treated TMD (SWEREG-TMD)

BMC Public Health. 2022 May 9;22(1):916. doi: 10.1186/s12889-022-13329-z.

ABSTRACT

BACKGROUND: Temporomandibular disorders (TMD) are common and affect approximately 10% of the adult population. TMD is usually associated with headache, pain in the masticatory muscles and/or the temporomandibular joint, clicking or crepitations during mandibular movement as well as painful and/or reduced mouth opening. This study aimed to investigate the level TMD-patients use social insurance benefits before and after their first time of diagnosis or first surgical event, compared to the general population. Furthermore, the aim was to investigate the differences in the use of social insurance benefits between surgically and non-surgically treated TMD-patients that were diagnosed in a hospital setting.

METHODS: All Swedish citizens aged 23-59 diagnosed with TMD in a hospital setting and/or surgically treated for the condition during 1998-2016 were identified via the Swedish National Board of Health and Welfare. A non-exposed comparison cohort was collected via the Total Population Registry. Outcome and sociodemographic data were collected via Statistics Sweden. Main outcome was annual net days on sick leave and disability pension five years before (-T5) and five years after (T5) diagnosis and/or surgical treatment (T0). Regression analysis was conducted with generalized estimated equations.

RESULTS: The study included 219 255 individuals (73% female) – 19 934 in the exposed cohort and 199 321 in the comparison cohort. The exposed group was classified into three subgroups: non-surgical, surgically treated once, and surgically treated twice or more. The mean annual net days of sick leave and disability pension combined during the ten-year follow-up was 61 days in the non-surgical group, 76 days in the surgically treated once group, and 104 days in the surgically treated twice or more subgroup. The corresponding number for the non-exposed comparison cohort was 32 days.

CONCLUSION: Patients diagnosed with TMD in a hospital setting are 2-3 times more dependent on the use of social benefits than the general population. The reliance on sick leave and disability pension is seen as early as five years before diagnosis, and the reliance remains after surgical treatment. The reliance is stronger in patients with several surgical interventions. These findings indicate that patients diagnosed with TMD constitute a patient group with a high burden of health issues causing long-term dependence on social security benefits.

PMID:35534826 | DOI:10.1186/s12889-022-13329-z

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Nevin Manimala Statistics

Changes in causes of pregnancy-related and maternal mortality in Zimbabwe 2007-08 to 2018-19: findings from two reproductive age mortality surveys

BMC Public Health. 2022 May 10;22(1):923. doi: 10.1186/s12889-022-13321-7.

ABSTRACT

BACKGROUND: Reducing maternal mortality is a priority of Sustainable Development Goal 3.1 which requires frequent epidemiological analysis of trends and patterns of the causes of maternal deaths. We conducted two reproductive age mortality surveys to analyse the epidemiology of maternal mortality in Zimbabwe and analysed the changes in the causes of deaths between 2007-08 and 2018-19.

METHODS: We performed a before and after analysis of the causes of death among women of reproductive ages (WRAs) (12-49 years), and pregnant women from the two surveys implemented in 11 districts, selected using multi-stage cluster sampling from each province of Zimbabwe (n=10); an additional district selected from Harare. We calculated mortality incidence rates and incidence rate ratios per 10000 WRAs and pregnant women (with 95% confidence intervals), in international classification of disease groups, using negative binomial models, and compared them between the two surveys. We also calculated maternal mortality ratios, per 100 000 live births, for selected causes of pregnancy-related deaths.

RESULTS: We identified 6188 deaths among WRAs and 325 PRDs in 2007-08, and 1856 and 137 respectively in 2018-19. Mortality in the WRAs decreased by 82% in diseases of the respiratory system and 81% in certain infectious or parasitic diseases’ groups, which include HIV/AIDS and malaria. Pregnancy-related deaths decreased by 84% in the indirect causes group and by 61% in the direct causes group, and HIV/AIDS-related deaths decreased by 91% in pregnant women. Direct causes of death still had a three-fold MMR than indirect causes (151 vs. 51 deaths per 100 000) in 2018-19.

CONCLUSION: Zimbabwe experienced a decline in both direct and indirect causes of pregnancy-related deaths. Deaths from indirect causes declined mainly due to a reduction in HIV/AIDS-related and malaria mortality, while deaths from direct causes declined because of a reduction in obstetric haemorrhage and pregnancy-related infections. Ongoing interventions ought to improve the coverage and quality of maternal care in Zimbabwe, to further reduce deaths from direct causes.

PMID:35534811 | DOI:10.1186/s12889-022-13321-7

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Nevin Manimala Statistics

Genome-wide identification of associations between enhancer and alternative splicing in human and mouse

BMC Genomics. 2022 May 9;22(Suppl 5):919. doi: 10.1186/s12864-022-08537-1.

ABSTRACT

BACKGROUND: Alternative splicing (AS) increases the diversity of transcriptome and could fine-tune the function of genes, so that understanding the regulation of AS is vital. AS could be regulated by many different cis-regulatory elements, such as enhancer. Enhancer has been experimentally proved to regulate AS in some genes. However, there is a lack of genome-wide studies on the association between enhancer and AS (enhancer-AS association). To bridge the gap, here we developed an integrative analysis on a genome-wide scale to identify enhancer-AS associations in human and mouse.

RESULT: We collected enhancer datasets which include 28 human and 24 mouse tissues and cell lines, and RNA-seq datasets which are paired with the selected tissues. Combining with data integration and statistical analysis, we identified 3,242 human and 7,716 mouse genes which have significant enhancer-AS associations in at least one tissue. On average, for each gene, about 6% of enhancers in human (5% in mouse) are associated to AS change and for each enhancer, approximately one gene is identified to have enhancer-AS association in both human and mouse. We found that 52% of the human significant (34% in mouse) enhancer-AS associations are the co-existence of homologous genes and homologous enhancers. We further constructed a user-friendly platform, named Visualization of Enhancer-associated Alternative Splicing (VEnAS, http://venas.iis.sinica.edu.tw/ ), to provide genomic architecture, intuitive association plot, and contingency table of the significant enhancer-AS associations.

CONCLUSION: This study provides the first genome-wide identification of enhancer-AS associations in human and mouse. The results suggest that a notable portion of enhancers are playing roles in AS regulations. The analyzed results and the proposed platform VEnAS would provide a further understanding of enhancers on regulating alternative splicing.

PMID:35534820 | DOI:10.1186/s12864-022-08537-1

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Nevin Manimala Statistics

A retrospective longitudinal cohort study of the clinical burden in myasthenia gravis

BMC Neurol. 2022 May 9;22(1):172. doi: 10.1186/s12883-022-02692-4.

ABSTRACT

BACKGROUND: Patients with generalized myasthenia gravis (MG) often experience debilitating exacerbations, with the possibility of life-threatening respiratory crises requiring hospitalization. Long-term longitudinal studies are needed to understand the burden of MG, including in patients whose disease is refractory to conventional treatment.

METHODS: A retrospective, longitudinal, cohort study was conducted of patients in England aged ≥ 18 years with treatment-refractory or non-refractory MG, using data recorded during 1997-2016 in the Clinical Practice Research Datalink and the Hospital Episode Statistics databases. A control cohort of patients without MG, matched to the patients in the treatment-refractory MG cohort, was also identified. Outcome measures included myasthenic crises, MG exacerbations, MG-related hospitalizations, comorbidities, and all-cause mortality. Descriptive statistics were calculated for the overall MG population. For continuous variables, between-cohort comparisons were made using t tests for normally distributed data and Mann-Whitney U tests for non-normally distributed data. For categorical data, the comparisons were made by chi-squared tests. Differences in clinical outcomes between cohorts were modeled using negative binomial regression.

RESULTS: A total of 1149 patients with MG were included. Overall, 18.4% of patients experienced myasthenic crises, 24.6% experienced exacerbations, and 38.6% underwent MG-related hospitalizations. Most of these events occurred within 2-3 years of diagnosis. Patients with MG refractory to conventional treatment (n = 66) experienced more exacerbations and MG-related hospitalizations than patients with non-refractory disease (n = 1083). Patients with refractory MG experienced a higher frequency of renal disease and hypertension compared with patients with non-refractory MG, and with matched patients without MG. They were also more likely to have diabetes and congestive heart failure than the matched controls. Rates of all-cause mortality during the follow-up period did not differ between patients with refractory MG and non-refractory MG.

CONCLUSIONS: These results show that conventional treatments for MG are not adequately managing patients’ symptoms and that patients with refractory MG are more likely to experience certain comorbidities than those with non-refractory MG or matched controls without MG. Future research should focus on the impact of newer targeted therapies on long-term clinical outcomes and comorbid conditions.

PMID:35534810 | DOI:10.1186/s12883-022-02692-4

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Nevin Manimala Statistics

The Importance of Statistical Significance in Drawing Conclusions in Clinical Research

Spine (Phila Pa 1976). 2022 May 1;47(9):E432. doi: 10.1097/BRS.0000000000004292. Epub 2021 Nov 12.

NO ABSTRACT

PMID:35533296 | DOI:10.1097/BRS.0000000000004292

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Nevin Manimala Statistics

Assessment of a New Approach Method for Grouped Chemical Hazard Estimation: The Toxicity-Normalized Species Sensitivity Distribution (SSDn)

Environ Sci Technol. 2022 May 9. doi: 10.1021/acs.est.1c05632. Online ahead of print.

ABSTRACT

New approach methods are being developed to address the challenges of reducing animal testing and assessing risks to the diversity of species in aquatic environments for the multitude of chemicals with minimal toxicity data. The toxicity-normalized species sensitivity distribution (SSDn) approach is a novel method for developing compound-specific hazard concentrations using data for toxicologically similar chemicals. This approach first develops an SSDn composed of acute toxicity values for multiple related chemicals that have been normalized by the sensitivity of a common species tested with each compound. A toxicity-normalized hazard concentration (HC5n) is then computed from the fifth percentile of the SSDn. Chemical-specific HC5 values are determined by back-calculating the HC5n using the chemical-specific sensitivity of the normalization species. A comparison of the SSDn approach with the single-chemical SSD method was conducted by using data for nine transition metals to generate and compare HC5 values between the two methods. We identified several guiding principles for this method that, when applied, resulted in accurate HC5 values based on comparisons with results from single-metal SSDs. The SSDn approach shows promise for developing statistically robust hazard concentrations when adequate taxonomic representation is not available for a single chemical.

PMID:35533293 | DOI:10.1021/acs.est.1c05632

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Nevin Manimala Statistics

Emerging canine leptospirosis in Sydney and the role of population demographics

Transbound Emerg Dis. 2022 May 9. doi: 10.1111/tbed.14591. Online ahead of print.

ABSTRACT

An outbreak of canine leptospirosis commenced in Sydney, Australia in 2017. The aim of this retrospective study was to determine if clusters of leptospirosis occurred during this outbreak, and if these were associated with host factors, to assist investigation of the drivers of emerging leptospirosis in this location site. Within the City of Sydney local government area, 13 cases were reported during the outbreak. Administrative data on the canine population were collected and mapped. Clusters of leptospirosis cases were detected using a retrospective space-time analysis and a discrete Poisson probability statistical model. Sydney dog population registration (55.6%, 95% confidence interval [CI] 51.8-58.1%) was lower than the Australian national average (80%). The distribution of dog types, based on the United Kennel Club standards, was significantly (P<0.0001) different to that of the national profile: there was a distinct preference in Sydney for companion dogs. The age distribution of dogs in Sydney did not reflect a typical right-skewed curve; instead, a relatively uniform distribution was observed between the age group of 1 to 8 years. A primary disease cluster (radius 1.1 km) in the eastern area of the Sydney City Council was identified (4 cases observed between 24 May and 9 August 2019 versus 0.10 cases expected), P = 0.0450. When adjusted for the age, breed type and sex distribution of the population, similar clusters were identified; in the case of age-adjustment, the spatio-temporal cluster identified was larger and of longer duration (seven cases observed between 28 June and 11 November 2019 versus 0.34 cases expected), P = 0.0025. The presence of clusters of canine leptospirosis in the City of Sydney during this outbreak, which persisted after adjustment for demographics (age, sex, breed type), suggest that environmental factors – rather than host or pathogen factors – might be responsible for the emergence of leptospirosis. Environmental factors that potentially might be linked to this outbreak of canine leptospirosis and the clusters observed require investigation. This article is protected by copyright. All rights reserved.

PMID:35533268 | DOI:10.1111/tbed.14591

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Nevin Manimala Statistics

Limits for the therapeutic application of the analytical anisotropic algorithm in the context of ablative lung radiotherapy near the minima of lung density and tumor size

J Appl Clin Med Phys. 2022 May 9:e13634. doi: 10.1002/acm2.13634. Online ahead of print.

ABSTRACT

PURPOSE: To systematically investigate the performance of the analytical anisotropic algorithm (AAA) within the extremes of small tumor volumes and near-minimum lung and tumor tissue densities in order to identify combinations of these parameters where the use of AAA could result in a therapeutically unacceptable loss of tumor coverage on an energy and fractionation-specific basis.

METHODS: Clinically appropriate volumetric modulated arc therapy (VMAT) treatment plans were generated with AAA for 180 unique combinations of lung density (0.05-0.30 g/cm3 ), tumor density (0.30-1.00 g/cm3 ), tumor diameter (0.5-2.5 cm), and beam energy (6 and 10 MV) and recomputed using the AcurosXB algorithm. Regression analysis was used to identify the strongest predictors of a reduction in biologically effective dose at a clinically relevant level (100 Gy BED10) for commonly utilized 1-5 fraction treatment regimens. Measurements were performed within a phantom mimicking the lower extremes of lung and tumor densities to validate AcurosXB as the approximate ground truth within these scenarios.

RESULTS: The strongest predictors of a statistically significant reduction in tumor coverage were lung density ≤0.15 g/cm3 , tumor diameter ≤10 mm, tumor density equal to 0.30 g/cm3 , and a beam energy of 10 MV. Overestimation of clinical target volume (CTV) D95% and CTV V100Gy (BED10) by AAA can exceed 30%-40% in some scenarios. Measurements supported AcurosXB as highly accurate even for these challenging scenarios.

CONCLUSIONS: The accuracy of AAA rapidly diminishes near the minima of clinical lung density, particularly in combination with small tumors and when using a photon energy of 10 MV. The magnitude of the effect can be more dramatic than previously reported data suggests and could potentially compromise the ablative qualities of treatments performed within these environments, particularly with less aggressive fractionation approaches.

PMID:35533238 | DOI:10.1002/acm2.13634